{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T14:55:08Z","timestamp":1786978508265,"version":"build-2736575974"},"reference-count":36,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2025,9,8]],"date-time":"2025-09-08T00:00:00Z","timestamp":1757289600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82173955"],"award-info":[{"award-number":["82173955"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal of Peptide Science"],"published-print":{"date-parts":[[2025,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Targeting thrombin to screen safe thrombin inhibitors from natural plants and animals is a critical direction in anticoagulant drug development. This study aimed to screen thrombin inhibitors from the nonbloodsucking leech\n                    <jats:italic>Whitmania pigra<\/jats:italic>\n                    (WP) and elucidate the mechanism of anticoagulation through a \u201ccomputation\u2010guided experimentation\u201d strategy. A peptide library was constructed from WP hydrolysates, and virtual screening was performed using molecular docking and dynamics simulations. A novel thrombin\u2010targeting anticoagulant peptide PEP\n                    <jats:sup>WP<\/jats:sup>\n                    (LRELEDALEQER) was screened out from the peptide library and validated through in\u00a0vitro\/in vivo experiments. PEP\n                    <jats:sup>WP<\/jats:sup>\n                    significantly prolonged thrombin time (TT) and prothrombin time (PT) in a dose\u2010dependent manner in\u00a0vitro, indicating its role in the common and extrinsic coagulation pathways. Surface plasmon resonance (SPR) analysis then confirmed strong thrombin binding (\n                    <jats:italic>K<\/jats:italic>\n                    <jats:sub>\n                      <jats:italic>d<\/jats:italic>\n                    <\/jats:sub>\n                    \u2009=\u20097.242\u2009\u00d7\u200910\n                    <jats:sup>\u22126<\/jats:sup>\n                    \u2009mol\/L). Furthermore, PEP\n                    <jats:sup>WP<\/jats:sup>\n                    prolonged TT while reducing blood viscosity in acute blood stasis rats. Finally, structural analysis revealed that PEP\n                    <jats:sup>WP<\/jats:sup>\n                    bound to Exosite II of thrombin. Arg233 and Arg101 were the key residues for the binding. In conclusion, PEP\n                    <jats:sup>WP<\/jats:sup>\n                    exhibited good anticoagulant activity and significant application potential.\n                  <\/jats:p>","DOI":"10.1002\/psc.70056","type":"journal-article","created":{"date-parts":[[2025,9,9]],"date-time":"2025-09-09T04:32:56Z","timestamp":1757392376000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Discovery of a Thrombin\u2010Targeting Anticoagulant Peptide From\n                    <i>Whitmania pigra<\/i>\n                    via a \u201cComputation\u2010Guided Experimentation\u201d Strategy"],"prefix":"10.1002","volume":"31","author":[{"given":"Yu\u2010Tong","family":"Hua","sequence":"first","affiliation":[{"name":"School of Chinese Materia Medica Beijing University of Chinese Medicine  Beijing China"},{"name":"State Key Laboratory for Quality Ensurance and Sustainable Use of Dao\u2010di Herbs, National Resource Center for Chinese Materia Medica China Academy of Chinese Medical Sciences  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rui\u2010Juan","family":"Dong","sequence":"additional","affiliation":[{"name":"School of Traditional Chinese Medicine Beijing University of Chinese Medicine  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yin","family":"Li","sequence":"additional","affiliation":[{"name":"School of Chinese Materia Medica Beijing University of Chinese Medicine  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhao\u2010Yu\u2010Qing","family":"Su","sequence":"additional","affiliation":[{"name":"School of Chinese Materia Medica Beijing University of Chinese Medicine  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Quan\u2010Cheng","family":"Xin","sequence":"additional","affiliation":[{"name":"School of Chinese Materia Medica Beijing University of Chinese Medicine  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